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C/EBP{alpha} in adipose tissue regulates genes in lipid and glucose metabolism and a genetic variation in C/EBP{alpha} is associated with serum levels of triglycerides.

Olofsson, Louise E ; Orho-Melander, Marju LU ; William-Olsson, Lena ; Sjöholm, Kajsa ; Sjöström, Lars ; Groop, Leif LU ; Carlsson, Björn ; Carlsson, Lena M S and Olsson, Bob (2008) In Journal of Clinical Endocrinology and Metabolism 93(12). p.4880-4886
Abstract
Context: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. Objective: To test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for association between a polymorphism in C/EBPalpha and metabolic parameters. Design and Methods: Adipose tissue C/EBPalpha mRNA expression was analyzed at four time points in obese subjects with (n=12) and without (n=12) the metabolic syndrome during caloric restriction (450 kcal/day for 16 weeks) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a... (More)
Context: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. Objective: To test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for association between a polymorphism in C/EBPalpha and metabolic parameters. Design and Methods: Adipose tissue C/EBPalpha mRNA expression was analyzed at four time points in obese subjects with (n=12) and without (n=12) the metabolic syndrome during caloric restriction (450 kcal/day for 16 weeks) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a genetic variation in C/EBPalpha (rs12691) and metabolic parameters was tested in the Swedish Obese Subjects (SOS) study (n=528) and replicated in Finnish individuals from the Botnia type 2 diabetes study (n=4866). Results: During caloric restriction, adipose tissue C/EBPalpha mRNA levels were reduced in subjects with the metabolic syndrome (P=0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBPalpha regulated the expression of ADIPOQ, HK2, LPL, DGAT 1 and 2, ABCD2, SLC27A2, CD36 and HSD11B1. Furthermore, the expression of the human homologues, except ADIPOQ, correlated to C/EBPalpha mRNA levels in human adipose tissue. The AA genotype of rs12691 was associated with higher serum triglyceride levels in the SOS study (P=0.022) and this association was replicated in the Botnia study (P=0.041). Conclusions: Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
93
issue
12
pages
4880 - 4886
publisher
Oxford University Press
external identifiers
  • wos:000261396900043
  • pmid:18765514
  • scopus:57349119903
  • pmid:18765514
ISSN
1945-7197
DOI
10.1210/jc.2008-0574
language
English
LU publication?
yes
id
9753b8d2-5229-4f79-afc6-8a13eedb861d (old id 1243473)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18765514?dopt=Abstract
date added to LUP
2016-04-01 13:41:54
date last changed
2024-04-24 12:50:39
@article{9753b8d2-5229-4f79-afc6-8a13eedb861d,
  abstract     = {{Context: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. Objective: To test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for association between a polymorphism in C/EBPalpha and metabolic parameters. Design and Methods: Adipose tissue C/EBPalpha mRNA expression was analyzed at four time points in obese subjects with (n=12) and without (n=12) the metabolic syndrome during caloric restriction (450 kcal/day for 16 weeks) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a genetic variation in C/EBPalpha (rs12691) and metabolic parameters was tested in the Swedish Obese Subjects (SOS) study (n=528) and replicated in Finnish individuals from the Botnia type 2 diabetes study (n=4866). Results: During caloric restriction, adipose tissue C/EBPalpha mRNA levels were reduced in subjects with the metabolic syndrome (P=0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBPalpha regulated the expression of ADIPOQ, HK2, LPL, DGAT 1 and 2, ABCD2, SLC27A2, CD36 and HSD11B1. Furthermore, the expression of the human homologues, except ADIPOQ, correlated to C/EBPalpha mRNA levels in human adipose tissue. The AA genotype of rs12691 was associated with higher serum triglyceride levels in the SOS study (P=0.022) and this association was replicated in the Botnia study (P=0.041). Conclusions: Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.}},
  author       = {{Olofsson, Louise E and Orho-Melander, Marju and William-Olsson, Lena and Sjöholm, Kajsa and Sjöström, Lars and Groop, Leif and Carlsson, Björn and Carlsson, Lena M S and Olsson, Bob}},
  issn         = {{1945-7197}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{4880--4886}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Clinical Endocrinology and Metabolism}},
  title        = {{C/EBP{alpha} in adipose tissue regulates genes in lipid and glucose metabolism and a genetic variation in C/EBP{alpha} is associated with serum levels of triglycerides.}},
  url          = {{http://dx.doi.org/10.1210/jc.2008-0574}},
  doi          = {{10.1210/jc.2008-0574}},
  volume       = {{93}},
  year         = {{2008}},
}